Different Association of Timp3, LIPC, FRK/COL10A, CEPT and CFHR1-3 Polymorphisms in Spanish Patients with Early, Wet and Atrophic Age-Related Macular Degeneration.

Abstract

Purpose: To determine if Single Nucleotide Polymorphisms (SNPs) from genes related to extracellular matrix homeostasis, such as TIMP3 (rs9621532) and FRK/COL10A (rs1999930), lipid metabolism like LIPC (rs10468017) and CEPT (rs3764261) and complement systems such as ΔCFHR1-3 (rs6677604) are associated with different forms of age-related macular degeneration (AMD) in Spanish patients.

Methods: Six hundred-eighty five patients with AMD (118 patients with early-AMD, 366 with wet-AMD and 201 with atrophic AMD) and 243 healthy controls were enrolled in the study. All the SNPs were analyzed by TaqMan® SNP genotyping assays. The chi-square test and multivariate logistic regression were used to analyze the association.

Results: The frequencies of protective alleles, A for ΔCFHR1-3 (rs6677604) and C for CEPT (rs3764261), were significantly lower in all AMD patient groups (early, wet and atrophic-AMD) vs. controls. The Odds Ratios (OR) obtained were 0.33 (95% confidence interval [CI], 0.19-0.58; P<0.001) and 0.40 (0.24-0.66; P<0.001), respectively for early-AMD, 0.36 (0.25-0.51; P<0.001) and 0.45 (0.28-0.73; P<0.001) respectively for wet-AMD and 0.34 (0.21-0.53; P<0.001) and 0.48 (0.30-0.77; P<0.001) respectively for atrophic-AMD. Moreover, the risk allele C for LIPC rs10468017 SNP showed significant association in patients with atrophic-AMD with an OR of 1.39 (1.01-1.91; P=0.049). The frequencies of FRK/COL10A1 (rs1999930) and TIMP3 (rs9621532) SNPs did not show statistical differences in any of AMD forms

Conclusions: Our data show that SNPs on the ΔCFHR1-3 and CEPT genes were associated with different forms of AMD while the SNP on LIPC gene is only associated with atrophic AMD in a Spanish population. These results suggest the important role of lipid metabolism and complement system genes in the development of AMD.

Keywords: 412 age-related macular degeneration • 539 genetics • 463 clinical (human) or epidemiologic studies: prevalence/incidence